Despite growing interest about osteoporosis in men, there is little data regarding the pathogenesis and risk factors for fracture in men, or effective diagnostic strategies in this population. To address these issues, the ongoing Osteoporosis in Men Study (MrOS) has successfully recruited over 6000 men over age 65 from 6 US clinical centers. MrOS collected extensive baseline measurements of anthropometric and health habits, as well as axial densitometry and lateral lumbosacral spine radiographs. Baseline QCT of the hip and spine, and sex hormones have been measured in subsets. Since the baseline visit, subjects have been followed for the occurrence of new fractures, and as of February 2005, 46 hip fractures and a total of 256 non-spine fractures have been reported and centrally adjudicated. Study participants will return to the clinical centers for repeat spine x-rays and densitometry beginning January, 2005, after a mean follow-up of 4.5 years. In this MrOS ancillary study, we plan to use archived serum and urine specimens from baseline and propose a prospective analysis of the relationship between bone turnover and incident vertebral, hip and any non-spine fracture using an efficient nested case-cohort study design. Our sampling scheme will take advantage of the many existing measurements in MrOS, including DXA, QCT and sex hormone levels. In addition, we will analyze the relationship between a new non-invasive biochemical index of bone collagen quality, type 1 collagen isomerization, and incident vertebral, hip and any non-spine fracture. Propective studies among older women suggest that both bone turnover and collage isomerization are independently associated with fracture risk, but such relationships have not been studied in men. Lastly, we plan to study bone turnover and bone loss, and determine which anthropometric, historical and health habit factors are associated with bone turnover. These analyses will address critical questions about the pathogenesis of spine and non-spine fracture in men, and will determine the clinical utility of bone turnover measurements in this population. [unreadable] [unreadable] [unreadable]